The proposed research is concerned with the mechanisms underlying differential gene expression and pattern formation in eukaryotic development and uses as a model system a devlopmentally regulated chromosomal locus of Drosophila melanogaster, the Notch locus. Mutations in this locus fundamentally affect the differentiation pattern of the embryo at the time of primary organogenesis causing the hypertrophy of the central nervous system. In spite of extensive embryological and genetic data regarding several alleles of this complex locus, there is no satisfactory explanation of either its biochemical nature or its action during development. The aim of this study is the molecular and developmental analysis of the Notch locus. The DNA sequences comprising the locus will be isolated using recombinant DNA techniques. The arrangement of the wild type sequences will be studied in detail and compared to that of mutant flies. Moreover, the transcriptional activity of Notch will be examined using various hybridization techniques, in vitro transcription and in situ hybridization of selected DNA fragments to tissue sections. Concurrently with the molecular analysis a developmental study will be undertaken. The internal and external morphology of wild type and Notch embryos will be examined using high resolution Nomarski optics. We will attempt to answer specific questions relating to the way Notch acts during embryonal development using temperature-sensitive mutations and genetic mosaics.